This application seeks support for continuation of our current grant entitled "Subclinical atherosclerosis in HIV+ black cocaine users". This study is the first NIH-funded study to investigate the effects of HIV and cocaine on subclinical atherosclerosis. We have not only demonstrated that both cocaine alone and HIV infection alone are associated with subclinical atherosclerosis, but also showed a trend suggesting concomitant exposure to both cocaine and HIV infection may further exacerbate the cardiac toxicity of either factor alone. However, to determine the joint effects of cocaine and HIV infection on subclinical disease, a larger sample size and longer observational periods are needed, and the effect of other factors, including antiretroviral regimens containing protease inhibitors(Pls) also needs to be investigated. Thus, in addition to continued follow-up of study participants in the current study (5-year follow-up rate >80%), we also will recruit additional study participants to obtain adequate power for testing the proposed hypotheses. The specific aims of this application are (1) To estimate the prevalence and incidence of coronary artery calcification (CAC) and the presence of coronary stenosis in black men and women with one of the following characteristics: cocaine(+) and HIV(+) and Pl(+); cocaine(+) and HIV(+) and Pl(-); cocaine(-) and HIV(+) and Pl(+); and cocaine(-) and HIV(+) and Pl(-); cocaine(+) and HIV(-); and cocaine(-) and HIV(-); (2) To investigate the combined effects of cocaine and HIV infection on subclinical atherosclerosis; (3) To investigate the association of inflammatory markers with subclinical atherosclerosis; (4) To investigate the effects of cocaine and antiretroviral therapy on subclinical atherosclerosis in HIV+ black men and women; and (5) To study whether and to what extent subclinical atherosclerosis influences left ventricular function (both systolic and diastolic). With the use of the most advanced CT system (a 64-slice multi-detector row CT), we will also be able to examine the effects of HIV and cocaine on the location, extent, and composition of coronary plaque. Thus, this study could lead to a breakthrough in research on cardiovascular complications of HIV infection and cocaine.